Application of Fmoc-SPPS, thiol-maleimide conjugation, and copper(i)-catalyzed alkyne-azide cycloaddition “click” reaction in the synthesis of a complex peptide-based vaccine candidate against group a Streptococcus

Abstract

Fmoc solid-phase peptide synthesis (SPPS) is the most common approach used to synthesize natural and unnatural peptides. However, the synthesis of sequences longer than 30–60 amino acids is associated with a drastic reduction in peptide quality. Thus, large and complex peptides are normally synthesized as fragments, which are then conjugated together. Here, we describe the synthesis of a large, branched peptide, a multi-epitope vaccine candidate against Group A Streptococcus, with the help of microwave-assisted Fmoc-SPPS, thiol-maleimide conjugation, and copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) “click” reaction.